This invention relates generally to in silico design of organisms and, more specifically to organisms having selected genotypes for the growth-coupled production of 3-hydroxypropionic acid (3-HP).
The compound 3-hydroxypropionic acid (3-hydroxypropionate or 3-HP) is a three-carbon carboxylic acid that has industrial potential as a building block for a number of commodity and specialty chemicals. Compounds that can be produced from 3-HP by chemical synthesis include polymer precursors such as acrylic acid, acrylamide, methyl acrylate, and 1,3-propanediol; chemical intermediates such as malonic acid, and a number alcohol esters of 3-HP. 3-HP itself also is used in the nutritional industry as a food preservative. Although the above compounds can be produced from petroleum feedstocks, the ability to produce the entire family of 3-HP derived products from a platform chemical, preferably made from renewable resources, would be useful. For these reasons, it is among the set of twelve compounds identified by the Department of Energy as highest priority for the development of bioprocesses out of over 300 evaluated candidates (DOE Report, “Top Value-Added Chemicals from Biomass”, 2004).
Several chemical synthesis routes have been described to produce 3-HP, and biocatalytic routes have also been disclosed (WO 01/16346 to Suthers et al). However, chemical synthesis of 3-HP is costly and inefficient.
Despite the efforts and reports purporting the development of biocatalytic routes for the production of 3-HP, the approaches employed have several drawbacks which hinder applicability in commercial settings. As described further below, the stains produced by the above methods can be unstable in commercial fermentation processes due to selective pressures favoring the unaltered or wild-type parental counterparts.
Thus, there exists a need for microorganisms having commercially beneficial characteristics that can efficiently produce commercial quantities of 3-HP. Obligatory linking biosynthesis of a desired product to optimal growth conditions is a further need that would be commercially beneficial. The present invention satisfies these needs and provides related advantages as well.